Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Remark
The preliminary amendment dated on Jan 08, 2024 has been acknowledge. Claims 1, 3-5 and 7-11 were amendment Claims 1-11 are pending.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 9 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Serve et al. (Anal Chem2015 Nov 3;87(21):10708-11. doi: 10.1021/acs.analchem.5b02681. Epub 2015 Oct 14.
Serve et al. teach a method using magnetic sulfated cellulose particles (MSCP) (beads) to purify influenza viruses comprise the following steps: 1). Making the MSCPs) with “Magne™ Protein A Beads 20% Slurry” (#G8781, Promega) was used as a backbone for sulfation as described in patent EP14175925.15 Briefly, 400 mg of the magnetic cellulose particles were added to a chloral sulfonic acid-pyridine reaction mixture (Claims 1:18.2) and incubated overnight at 35°C. Then the supernatant was decanted and the MSCP were washed with MQ water to remove any residual pyridine. Finally, the MSCP were resuspended in 20% ethanol to get a 50 vol% MSCP solution for storage; 2). Virus purification and concentration with magnetic sulfated cellulose particles. 1.75 ml of the 50 vol% MSCP in 20% ethanol(aq) solution were washed three times with 10 mM Tris HCl(aq) pH 7.4. CVH was diluted with 10 mM Tris-HCl(aq) pH 7.4 1:3 to decrease the salt content of the sample for optimal virus binding to the MSCP. Fifteen ml of the diluted virus solution was incubated with the washed MSCP for 1 min under gentle mixing. Then the supernatant was discarded and bound influenza A virus particles were eluted from the MSCP with 1 ml of 0.6 M NaCl(aq) 10 mM Tris-HCl(aq) pH 7.4. Final ly, the MSCP were regenerated with 15 ml 2 M NaCl(aq), 10 mM Tris-HCl(aq) pH 7.4 for 10 min and conditioned for the next virus purification by washing three times with 15 ml 10 mM Tris-HCl(aq) pH 7.4. The virus purification by the MSCP method was carried out simultaneously for all six CVH samples and took approximately 10 minutes. Therefore, claims 1 and 9 are anticipated by the cited reference.
Claims 1, 5-9 and 11 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by (WO 2020/126730A1) to Jansson et al.
The rejected claims 1 and 5-8 are draw to a method for virus purification comprising the following steps: a) adding magnetic beads to a crude cell lysate suspension comprising target virus; b) homogenizing and incubating said suspension to allow binding of said target virus to ligands on said magnetic beads; c) capturing said magnetic beads; d) removing supernatant from said magnetic beads; e) washing and repeating steps c)-d); and f) adding elution buffer, and collecting eluate containing target virus, wherein the magnetic beads comprise 2-6% agarose or 3-5% agarose, or 4% agarose wherein ligands are quaternary trimethylamine (Q) and/or dextran sulfate (DxS) (claim 5), wherein the ligands are provided on dextran extenders. (claim 6), wherein the target virus is adenovirus and the ligands are Q-ligands. (Claim 7), wherein the target virus is influenza virus and the ligands are S-ligands (claim 8), Method according toclaim 1,wherein said binding of target virus to ligands occurs within 30 minutes, within 15 minutes, within 5 minutes, or within 1 minute (claim 9). wherein the magnetic beads comprise 4 % agarose and have an average diameter of up to claim 1,wherein step e) is repeated up to five times. (Claim 11 ).
WO 2020/126730A1 to Jansson et al. disclose a method for purify viruses, specifically adenoviruses with agarose comprising pore optionally adding a magnetic material to form a water (W) -immedicable oil phage (O) in which at least one emulsoid dissolve. Furthermore, a ligands that can bind to the virus is coupled to emulsified beads formed. Please see the section of the summary of the invention, which cites:
In one aspect, the present invention provides a method of preparing a porous cross-linked agarose gel beads comprising the steps of:
a) Emulsifying,
(i) preparing an agarose aqueous phase having an agarose concentration of 0.3- 0.8% w/v (W),
(ib) optionally adding a magnetic material, such as magnetite,
(ii) preparing a water-immiscible oil phase (O) in which at least one emulsifier is
dissolved,
(iii) mixing the water phase (W) and the oil phase (O) to obtain a W/O emulsion,
(iv) allowing the W/O emulsion to form beads.
b) Cross-linking the emulsified agarose one or several times by reacting the beads with a cross-linking agent,
c) Optionally coupling of ligands.
In another aspect, the present invention relates to porous cross-linked agarose gel particles obtainable by the method disclosed above.
In a further aspect, the present invention relates to porous, spherical cross-linked agarose gel beads, having an agarose concentration of about 0.3-0.8% w/v or a dry weight of 5-15 mg/mL, and optionally comprising a magnetic material. In a further aspect, the present invention relates to a separation matrix comprising porous, cross-linked agarose gel beads prepared according to the method described above.
In a further aspect, the present invention relates to a method of separating particles in a liquid from other components in the liquid comprising the steps of:
a) contacting the liquid with the separation matrix as described above to allow adsorption and/or absorption of the particles,
b) optionally washing the separation matrix,
c) eluting the particles from the matrix by adding a liquid that releases the particles, d) recovering the particles from the eluate.
In a further aspect, the present invention relates to the use of porous cross-linked agarose gel beads as described above as a matrix in affinity chromatography, ion exchange
chromatography, hydrophobic interaction chromatography, reversed phase chromatography, chelate chromatography, covalent chromatography, size exclusion chromatography.
The beads according to the invention are especially useful for the separation of large particles, such as particles having a size of about 20-400 nm for the inner core. In particular, the beads are useful for the separation of virus particles, such as virus particles in a biological sample. The pores are large enough that the particles can interact with internal pore surfaces and the beads are sufficiently resilient for mechanical handling, particularly in batch adsorption processes where beads comprising magnetic material can be used.
Furthermore, the cited reference also teaches that: “The porous cross-linked agarose gel beads according to claim 8, wherein the ligands are quaternary amine ligands, sulphate ligands, virus affinity ligands and/or multimodal ligands (Claim 9). For instance, wherein the ligands are quaternary amine ligands (claim 10) wherein the ligands are attached via extenders. wherein the extenders are carbohydrate molecules, e.g. dextran molecules.(Claims 11-12). The porous cross-linked agarose gel beads further comprising magnetic particles, e.g. magnetite. (claim 13). In particular, the cited reference teaches that Most commonly, separation/isolation of virus is effected by I EC using a matrix with ligands to which the specific virus has affinity. Suitable ligands for virus separation using I EC include sulfate ligands (S- ligands) and quaternary amine ligands (Q-ligands). For instance, influenza virus is typically separated/isolated by I EC using a matrix to which S-ligands are linked, whereas separation of adenovirus is performed using a Q-linked matrix, such as a cross-linked agarose matrix to which Q-ligands are linked either directly or via dextran extenders.
Therefore, the cited reference anticipates claims 1, 5-9 and 11.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite in that it fails to point out what is included or excluded by the claim language. This claim is an omnibus type claim. In particular, it is unclear what is the size of the magnets beads? First of all , It is confusing how an average diameter is more than one and unclearly defined size too.
Claims 2-3 are indefinite because it recites an improper Markush group. The applicant is referred to MPEP 2173.05(h) and advised to reformat the claim to read “wherein R is a material selected from the group consisting of A, B, C and D” or “wherein R is A, B, C or D”. In the instant case, the claim is cited with more than one option such as or mutein, or a biologically active fragment …. or multiple subunit of …… It is unclear and confusing which ono is entitled for the in that the Markush claim should be cited clearly there is only one alteration is intended. Therefore, the metes and bounds of the claimed subject matter is not vague and defined.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite in that it fails to point out what is included or excluded by the claim language. This claim is an omnibus type claim. In particular, it is unclear what is the size of the magnets beads? First of all , It is confusing how much the magnetic beads are added into the
Claim 4 is indefinite because it recites an improper Markush group. The applicant is referred to MPEP 2173.05(h) and advised to reformat the claim to read “wherein R is a material selected from the group consisting of A, B, C and D” or “wherein R is A, B, C or D”. In the instant case, the claim is cited with more than one option such as or mutein, or a biologically active fragment …. or multiple subunit of …… It is unclear and confusing which ono is entitled for the in that the Markush claim should be cited clearly there is only one alteration is intended. Therefore, the metes and bounds of the claimed subject matter is not vague and defined.
MPEP 21703.05 (h) cites: “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. If a claim is intended to encompass combinations or mixtures of the alternatives set forth in the Markush grouping, the claim may include qualifying language preceding the recited alternatives (such as "at least one member" selected from the group), or within the list of alternatives (such as "or mixtures thereof"). Id. at 1281.
Conclusion
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
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